Abstract

Isoflavones possess a wide range of physiological effects. However, it is still unclear whether isoflavones can promote milk synthesis in mammary gland. This study aimed to determine the effects of a main soy isoflavone, daidzein, on milk synthesis and proliferation of mammary epithelial cells (MECs) and reveal the underlying molecular mechanism. Primary bovine MECs were treated with different concentrations of daidzein (0, 5, 10, 20, 40, and 80 μM). Daidzein dose-dependently promoted α- and β-casein and lipid synthesis, cell cycle transition, and cell amount, with the best stimulatory effect at 20 μM. Daidzein also stimulated mTOR activation and Cyclin D1 and SREBP-1c expression. Daidzein induced the expression and nuclear localization of estrogen receptor α (ERα), and ERα knockdown blocked the stimulation of daidzein on these above signaling pathways. ERα knockdown also abolished the stimulation of daidzein on NFκB1 expression and phosphorylation, and NFκB1 was required for daidzein to enhance the mTOR, Cyclin D1 and SREBP-1c signaling pathways. In summary, our findings reveal that daidzein stimulates milk synthesis and proliferation of MECs via the ERα-dependent NFκB1 activation.

摘要

异黄酮具有广泛的生理作用。然而，异黄酮是否能促进乳腺的乳汁合成仍不清楚。本研究旨在确定主要大豆异黄酮黄豆苷元对乳汁合成和乳腺上皮细胞 (MEC) 增殖的影响，并揭示其潜在的分子机制。用不同浓度的黄豆苷元（0、5、10、20、40 和 80 μM）处理原代牛 MEC。Daidzein 剂量依赖性地促进 α- 和 β- 酪蛋白和脂质合成、细胞周期转换和细胞数量，在 20 μM 时具有最佳刺激作用。黄豆苷元还刺激 mTOR 活化和 Cyclin D1 和 SREBP-1c 表达。黄豆苷元诱导雌激素受体α（ERα）的表达和核定位，和 ERα 敲低阻断了黄豆苷元对上述信号通路的刺激。ERα 敲低也消除了黄豆苷元对 NFκB1 表达和磷酸化的刺激，并且 NFκB1 是黄豆苷元增强 mTOR、Cyclin D1 和 SREBP-1c 信号通路所必需的。总之，我们的研究结果表明，黄豆苷元通过 ERα 依赖性 NFκB1 激活来刺激乳汁合成和 MEC 的增殖。